Immonium salts and derivatives thereof

ABSTRACT

There are provided: novel aryloxy immonium salts, prepared by the reaction of their corresponding haloformates with amides; and phenolic compositions corresponding to the aryloxy immonium salts. These novel aryloxy immonium salts and their corresponding phenolic compositions have utility as chemical intermediates, antioxidants, stabilizers and antibacterials.

This is a division of application Ser. No. 355,825, filed Apr. 30, 1973,now abandoned which is a division of copending application Ser. No.663,897 filed Aug. 28, 1967.

This invention relates to novel compounds, their preparation and uses aschemical intermediates, antioxidants, stabilizers and antibacterials.

More particularly, it relates to the preparation of a novel and unusualclass of immonium salts and their utility as chemical intermediates inreactions to produce phenolic compositions.

It is an object of this invention to provide novel immonium salts andprocesses for preparing them.

Another object of this invention is to prepare aryloxy substitutedimmonium salts.

A further object of the invention is to provide novel immonium saltsuseful as chemical intermediates, antioxidants, stabilizers andantibacterials.

An additional object of this invention is to provide phenoliccompositions derived from the novel immonium salts of this invention,which compositions are useful as antioxidants, stabilizers andantibacterials.

Another object of this invention is to provide novel processes forpreparing phenolic compositions utilizing the novel immonium salts ofthis invention as chemical intermediates.

Still further objects and the scope of the present invention will becomeapparent from the detailed description given. It should be understood,however, that the detailed description and specific examples, whileindicating preferred embodiments of the invention, are given by way ofillustration only, since various changes and modifications within thespirit and scope of the invention will become apparent from thisdescription to those skilled in the art.

In accordance with this invention, immonium salts have been prepared ofthe general formula: ##SPC1##

Wherein a, b, c, d, and e are independently selected from the groupconsisting of hydrogen, hydrocarbyl, α-haloalkyl, halogen and nitro; Ris selected from the group consisting of hydrogen, alkyl and aryl; R'and R" are independently selected from the group consisting of hydrogenand alkyl, preferably of 1 to 12 carbon atoms, and X is selected fromthe group consisting of bromine, chlorine and fluorine; the hydrocarbylgroups and α-haloalkyl are of from one to thirty carbon atoms, andpreferably of 1 to 12 carbon atoms, and most preferably of 1 to 6 carbonatoms, and aryl is selected from the group phenyl and naphthyl.

By the term hydrocarbyl is meant the radical obtained by removal of onehydrogen atom from a hydrocarbon and thus encompasses alkyl, alkenyl,aryl, cycloalkyl, cycloalkenyl, alkylaryl and arylalkyl.

All of the above described radicals encompass hydrocarbon radicals offrom about one to about thirty carbon atoms, with the term arylencompassing benzene and naphthalene radicals. The above radicals aremore fully described here by definite examples.

This invention also includes the process of preparing compositions ofFormula (I) which comprises reacting compositions having the formula:##SPC2##

with compositions of the formula: ##SPC3## ##EQU1## wherein a, b, c, d,e, R, R', R", and X are as above described, and Q is selected from thegroup consisting of carbon and sulfur.

The preparation of the novel immonium salts of this invention isillustrated by the following general equation: ##SPC4##

The above equation (IV) illustrates the novel process of this invention,wherein aryl haloformates in reaction with amides or substituted amidesform the novel aryloxy substituted immonium salts of this invention,together with carbon dioxide or sulfur dioxide. In a more restrictedfashion, this invention includes preferred novel compositions of thefollowing general formula: ##SPC5##

wherein A, B, and E are independently selected from the group consistingof hydrogen, alkyl, and α-haloalkyl, the alkyl and α-haloalkyl groupsbeing from one to thirty carbon atoms, but preferably of 1 to 12 carbonatoms, and most preferably of 1 to 6 carbon atoms.

The present process for preparing compositions of Formula (V) comprisesreacting a haloformate composition of the formula: ##SPC6##

with dimethyl formamide wherein A, B, and E are as above described.

Used as chemical intermediates, the instant novel compounds of thisinvention of Formula (I) participate in the process for preparingphenolic compositions of formula: ##SPC7##

which comprises reacting compositions of Formula (I) with substantiallyequimolar quantities of compositions of formula GOH, wherein a, b, c, d,e, R, R', R", and X are as defined above; and G is selected from thegroup hydrogen and lower alkyl of 1 to 6 carbon atoms.

Another novel process for preparing compositions of Formula (VII)comprises reacting compositions of Formula (II) with dihydrocarbylsulfoxides such as dimethyl sulfoxide and the like.

Thus, the novel process for preparing phenolic compositions of Formula(VII), which comprises reacting the novel compositions of Formula (I)used as chemical intermediates, is illustrated by the following generalequation: ##SPC8##

It is seen from the above equation (VIII) that GOH, being water or alower alkanol, reacts with compositions of Formula (I) to formcompositions of Formula (VII), hydrogen halide or alkyl halide, and thecorresponding amide.

In the above Equation (VIII), the reactants are utilized instoichiometric, less than, or greater than the stoichiometricproportions to effect the novel compositions of Formula (VII).

Thus, in the above Equation (VIII) the composition GOH may be used at0.1 to 100 times the stoichiometric proportions, more preferably at 0.3to 10 times, although approximately stoichiometric proportions are mostpreferred. Such excesses or deficiencies may also be employed in theother reactions recited in this specification, wherein stoichiometricproportions are preferred.

In another aspect, this invention includes a process for preparingphenolic compositions of formula: ##SPC9##

by reacting compositions of Formula (V) with equimolar quantities ofmethanol wherein A, B, and E are as described. With reference to thepreparation of the phenolic compositions of Formula (IX) or (VII) above,less than or greater than equimolar quantities of reagent GOH may beused, although stoichiometric quantities are preferred. It is obviousthat if less than equimolar quantities of reagent GOH are used,decreased quantities of the above described phenolic compositions areproduced.

The present invention also includes the process for preparing phenoliccompositions of formula: ##SPC10##

wherein at least one of the group t, p, q, r, and u is J--CH₂ -- andwherein t, p, q, r, and u are selected from the group consisting ofhydrogen, hydrocarbyl, alkyl, α-haloalkyl, halogen, nitro, and J--CH₂--, wherein the nucleophile J-- is selected from the group consisting ofalkoxy, cyano, dialkylphosphono, bis(alkylcarbonyl), amino, alkylthio,and nitrato, and wherein the sum of the J--CH₂ --'s is from one to two,which comprises reacting compositions of Formula (VII), wherein a, b, c,d, and e are independently selected from the group consisting ofhydrogen, hydrocarbyl, alkyl, haloalkyl, halogen, and nitro, where thesum of the α-haloalkyls is from one to two, and the number ofα-haloalkyls is equal to the number of J--CH₂ --'s in the phenoliccomposition of Formula (X), with a nucleophilic reagent of formula J-Dwherein J-D is selected from the nucleophile group of water, alkanols,alkali metal cyanides, trialkyl phosphites, alkanediones, amines,mercaptans, and silver nitrate.

The novel process for preparing phenolic compositions of Formula (X)thus includes a reaction of the nucleophilic reagent of Formula J-D withthe α-haloalkyl group of the phenolic compositions of Formula (VII). Aspecific example of this novel process is illustrated in Equation (XI)below, which illustrates the process for preparing p-methoxymethylphenol which comprises reacting p-chloromethyl phenol with methanol.##SPC11##

The novel process of this invention for preparing phenolic compositionsof Formula (X) may also be effected by consecutive reactions startingwith compositions of Formula (I) or with the haloformates of Formula(II).

Thus, one of the preferred processes of this invention comprises thenovel reaction of a starting haloalkyl aryl haloformate or halosulfiteFormula (II) with one mole of an amide Formula (III) to produce an insitu novel immonium salt Formula (I). This immonium salt is thensubsequently reacted with a composition GOH (described above) to form insitu an intermediate phenolic composition Formula (VII). Theintermediate phenolic composition of Formula (VII) is then subsequentlyreacted with a nucleophile of formula J-D described above to effect thefinal J--CH₂ -- substituted phenolic composition, wherein the sum of theJ--CH₂ --'s is one or two.

One of the preferred processes of the invention thus comprises thefollowing steps:

1. The α-halomethyl aromatic haloformate (as a chloromethyl phenylchloroformate) and an equivalent amount (sometimes less or greater thanan equivalent amount is used) of an amide (often dimethyl formamide)were reacted by stirring in a suitable solvent (as acetonitrile) for asuitable period to finish the reaction (often about an hour). The amideused as a reactant in a suitable solvent may be used in the range of 0.1to 100 times the stoichiometric proportion, more preferably at .3 to 10times, although approximately stoichiometric proportions are mostpreferred.

In some cases, however, the amide may serve as a reaction solvent inwhich it then may be used in excess in the range of 1.1 to 1000 timesthe stoichiometric proportion, more preferably at 3 to 100 times,although approximately 5 to 50 times the stoichiometric proportions aremost preferred.

The time of reaction may vary from 5 minutes to 48 hours, morepreferably from 30 minutes to 24 hours, although approximately 1/2 to 2hours are preferred. The temperature of this step may vary from thefreezing point to the boiling point of the solvent, but ambienttemperatures are preferred. The most preferred temperature range is from25°-30°C. The solvent here may be any solvent such as acetonitrile,benzene, toluene, cyclohexane, propionitrile, and the like which willeffect solution of the reactive ingredients without participating in thereaction. Acetonitrile is often the preferred solvent.

2. The above prepared immonium salt (which may be isolated if desired)was treated with an equivalent amount (sometimes less or greater than anequivalent amount is used) of composition GOH (methanol often preferred)and the mixture was stirred for a suitable period (often one hour) toprepare the corresponding phenolic composition. The temperature + timepreferences of Step 1 are retained for Step 2. The amount of GOH whereinGOH is used as a reactant in a suitable solvent (described in Step 1)follows exactly the amide preferences of Step 1.

The term "excess" in the following table for CH₃ OH refers to the use ofGOH as a reaction solvent and the amide reaction solvent preferences ofStep 1 are retained.

3. The above prepared phenolic composition was treated with anequivalent amount (sometimes less or greater than an equivalent amountis used) of a nucleophile, and the reaction mixture was stirred and/orheated to effect reaction. The amount of nucleophile wherein thenucleophile is used as a reactant in a suitable solvent (described inStep 1) follows exactly the amide preferences of Step 1.

The term "excess" in the following table under nucleophile refers to theuse of excess nucleophile as a reaction solvent and the amide reactionpreferences of Step 1 are retained. The final nucleophile substitutedphenolic composition may be isolated by suitable means as illustrated inthe examples. The temperature ranges here may vary from the freezingpoint to the boiling point of the reaction mixture, but temperatures inthe range of ambient to reflux are preferred. The reaction timepreferences of Step 1 are retained for Step 3.

The table below summarizes some of the effected embodiments of thisinvention -- reactions of the chloromethylphenols. Similar reactions areeffected if other corresponding haloalkyl haloformates are used.

In the table below on reactions of chloromethylphenols the numbersindicate the molar ratio of the reagent to the starting material, butoften a greater or smaller molar ratio may be used if desired asdescribed above in the preferred ranges.

The triethyl amine in the second example of this table is not a truenucleophile here but merely an HCl acceptor.

The term DMF in the following table refers to dimethyl formamide.##SPC12##

The above described nucleophilic reagent of formula J-D may also beselected from the nucleophile group of silver nitrate, mercaptans, andamines.

Using silver nitrate as an embodiment of a nucleophile in reaction withthe α-haloalkylaryls of Formula (VII), wherein the sum of theα-haloalkyls is selected from the group one and two, produces thecorresponding α-nitratoalkylaryl phenolic composition of Formula (X).

In accordance with the above, the use of mercaptan as a nucleophileresults in the corresponding α-alkylthiomethylene aryl phenoliccomposition.

Also in accordance with the above, the use of amines or ammonia as thenucleophile effects the corresponding α-amino alkyl aryl phenoliccomposition where the amino radical is selected from the group --NR_(h)R'_(h) and --^(+NR) _(h) R'_(h) R"_(h) wherein R_(h), R'_(h), and R"_(h)are independently selected from the group of hydrogen, alkyl, aryl, andhydrocarbyl. The carbon atom preferences for the hydrocarbyl group ofFormula (I) are retained.

The starting haloformates of this invention embraced by Formula (II) canbe prepared, for example, by phosgenation of the appropriate phenol. Theα-haloalkyl haloformates are prepared by free radical chlorination ofthe above prepared haloformate with phosphorus trichloride, sulfurylchloride, benzamide, and benzoyl peroxide. Examples 1 through 4 giveillustrations of the preparations of the starting haloformates.

Typical examples of suitable haloformates embraced by Formula (II), ormore restrictedly, by Formula (VI), include phenyl chloroformate,p-cresyl chloroformate, 2,6 xylyl chloroformate, 2-chloro-p-cresylchloroformate, α-chloro-2,6-xylyl chloroformate, m-cresyl chloroformate,m-cresyl bromoformate, o-cresyl chloroformate, o-cresyl bromoformate,p-chloromethyl-phenyl chloroformate, m-chloromethyl-phenylchloroformate, o-chloromethyl-phenyl chloroformate,o-chloromethyl-phenyl bromoformate, 2,6-dichloromethyl-phenylbromoformate, phenyl bromoformate, m-cresyl fluoroformate,p-bromomethyl-phenyl chloroformate, m-bromomethyl phenyl chloroformate,o-bromomethyl-phenyl chloroformate, 3,5-xylyl chloroformate, 3,5-xylylbromoformate; α,α" dichloro-3,5-xylyl chloroformate;α,α'-dibromo-3,5-xylyl chloroformate; α,α'-dibromo-3,5-xylylbromoformate; 3,4-xylyl chloroformate; α,α'-dichloro-3,4-xylylchloroformate; α,α'-dibromo-3,4-xylyl bromoformate, p-chloro-o-benzylchloroformate; 3,5-diisopropylphenyl chloroformate,α-chloro-3,5-diisopropyl chloroformate, α-bromo-3,5-diisopropylphenylchloroformate, 2-allylphenyl chloroformate, 2-(2,3-dichloropropyl)phenylchloroformate and 2-(2,3-dibromopropyl)phenyl bromoformate and mixturesthereof. Typical examples of suitable halosulfites of this inventionembraced by Formula (II) include phenyl chlorosulfite, o-cresylchlorosulfite, examples formed by replacing carbon in the listing ofhaloformates above with sulfur to form the corresponding halosulfites,and mixtures thereof.

Suitable amides for this invention include compositions having theFormula III which include dimethyl formamide, dimethyl acetamide,formamide, acetamide, propionamide, n-butyramide, isobutyramide,stearamide, benzamide, nicotinamide, acetanilide, acetophenetidine,benzanilide, urethane, urea, carbanilide, N-ethyl-2-naphthamide,N,N-dimethyl acetamide, p-toluanilide, benzo-p-toluidide,pentadecanamide, 4-methyl-2-pentenamide, cyclo hexane carboxamide,melanamide, 2-acetamide quinoline, 4-benzamido pyridine, 4-butyerylmorpholine, α-valerolactam, and mixtures thereof.

The immonium salts of this invention include those of the generalFormula (I) and the more specific Formula (V).

Typical examples of suitable aryloxy-substituted immonium salts includethe immonium salt of dimethyl formamide and α-chloro-p-cresylchloroformate, the immonium salt of dimethyl formamide and p-cresylchloroformate; the immonium salt of dimethyl formamide andα,α'-dichloro-2,6-xylyl chloroformate; the immonium salt of dimethylformamide and o-cresyl chloroformate; the immonium salt of dimethylformamide and p-chloro-o-benzyl chloroformate and m-cresylchloroformate, the immonium salt of dimethyl formamide andα-chloro-o-cresyl chloroformate; the immonium salt of dimethyl formamideand α-chloro-m-cresyl chloroformate; the immonium salt of dimethylacetamide and α,α'-dibromo-2,6-xylyl bromoformate and mixtures thereof.

Other suitable examples of aryloxy-substituted immonium salts includeall the examples formed by any combination of a compound selected fromthe list of the haloformates or halosulfites in combination with acompound selected from the list of the amides and mixtures thereof.

Typical examples of the phenolic compositions embraced by generalFormula (VII) and the more specific Formula (IX) include the following:p-chloromethyl phenol, m-chloromethyl phenol, o-chloromethyl phenol,p-bromomethyl phenol, 2-methyl-6-chloromethyl phenol,2-methyl-6-bromomethyl phenol, 2,6-dichloromethyl phenol,p-chloro-o-benzyl phenol, 2,6-dibromomethyl phenol, 2,6-difluoromethylphenol, o-cresol, m-cresol, p-cresol, 2,6-xylenol and mixtures thereof.

Other typical examples of suitable phenolic compositions of generalFormula (VII) may be derived from the list of the haloformates bysubstituting the phenolic hydroxyl group for the haloformate group andmixtures thereof.

Typical examples of compositions of Formula GOH described above in theformation of phenolic compositions of Formula (VII) include water,deuterium oxide and the lower alkanols, where G is selected from thegroup hydrogen and lower alkyl, and lower alkyl may be more specificallydefined as containing from one to six carbon atoms. Thus, typicalexamples included in the group of lower alkanols include methanol,ethanol, propyl alcohol, isopropyl alcohol, butyl alcohol, isobutylalcohol, amyl alcohol, isoamyl alcohol, hexyl alcohol, isohexyl alcohol,t-butyl alcohol, hexanol-2 and mixtures thereof.

Typical examples of nucleophilic reagents of general Formula J-D used inthe preparation of phenolic compositions of general Formula (X) areselected from the group of alkanols, alkali metal cyanides, mercaptans,silver nitrate, trialkyl phosphites, amines and alkanediones.

The alkanols of general formula ROH, where R has the carbon atompreferences of the hydrocarbyl radical of Formula (I), include the abovementioned lower alcohols and other alcohols such as octanol, decanol,isodecanol, lauryl alcohol, stearyl alcohol and mixtures thereof.

The alkali metal cyanides are included in the group lithium cyanide,sodium cyanide, potassium cyanide, rubidium cyanide and cesium cyanide.

Typical examples of suitable trialkyl phosphites include phosphites ofgeneral Formula (RO)₃ P, wherein R has the carbon atom preferences ofthe hydrocarbyl radical of Formula (I), and suitable examples includetrimethyl phosphite, triethyl phosphite, tripropyl phosphite, tributylphosphite, diethylmethyl phosphite, trihexyl phosphite, dibutyldecylphosphite, trinonyl phosphite and mixtures thereof.

Typical examples of alkanediones include more specifically the group ofα,γ- diketones which include acetyl acetone, 2,4-pentanedione,2,4-hexanedione, 2,4-octanedione and mixtures thereof.

Typical examples of suitable nucleophilic amines include, in addition toammonia, methylamine, dimethylamine, trimethylamine, ethylamine,diethylamine, triethylamine, dipropylamine, isopropylamine, allylamine,diallylamine, dibutylamine, isobutylamine, sec-butylamine, t-butylamine,amylamine, cyclohexylamine, dicyclohexylamine, 2-aminoheptane,2-amino-4-methylhexane, decylamine, dioctylamine, trioctadecylamine,tallow amine and mixtures thereof.

Typical examples of suitable nucleophyl mercaptans include the entitieswhere sulfur is substituted for the oxygen of the alkanols. In addition,suitable mercaptans include methyl mercaptan, ethyl mercaptan, propylmercaptan, butyl mercaptan, amyl mercaptan, hexyl mercaptan, heptylmercaptan, octyl mercaptan, nonyl mercaptan, 2-mercapto-ethanol,2,3-dimercapto-1-propanol and mixtures thereof.

Typical examples of suitable silver nitrate type nucleophile compoundsinclude silver nitrate and other soluble salts of group Ib of theperiodic table which form insoluble metal halides, especially insolublemetal chlorides, and mixtures thereof.

Numerous examples of the novel aryloxy substituted immonium salts ofthis invention may be obtained from any combination of the above listedhaloformates and the above listed amides.

The above synthesized compositions of Formula (I) may be utilized tosynthesize suitable products of Formula (VII) by reaction of the abovecompositions of Formula (I) with compositions of Formula GOH, describedabove.

The synthesized compositions of Formula (VII) may be utilized tosynthesize compositions of Formula (X) by reaction of the compositionsof Formula VII with the above described examples of nucleophilicreagents of Formula J-D.

It is noteworthy that processes of this invention enable one to preparephenolic compositions which are often unstable when prepared by othersynthetic methods.

Also novel and noteworthy is the application of our novel immonium saltsas antioxidants, stabilizers, and antibacterials. These utilities alsoapply to the phenolic compositions derived from the novel immonium saltsof this invention. Surprisingly, the immonium salts of this inventionhave utility not only because of their intrinsic chemical structure butalso because of their slow atmospheric hydrolysis to their correspondingphenolic compositions. In this way, they are particularly effective inapplications as antioxidants, stabilizers, and antibacterials. Theseutilities also apply to the phenolic compositions of Formula (VII),Formula (IX) and Formula (X). The phenolic compositions of Formula(VII), (IX), and (X) -- and their corresponding immonium saltcompositions are particularly effective antibacterials againstEberthella typhosa or Staphylococcus aureus. Most effective andpreferred are the alkyl, halogen, and/or arylalkyl substituted phenoliccompositions and their corresponding immonium salts.

For example, the immonium salt of dimethyl formamide andp-chloro-o-benzyl chloroformate can be particularly effective andpreferred as a slow acting and excellent bactericide. This immonium saltused by itself or in solution, dispersion, or emulsion in a non-aqueous,aqueous/non-aqueous, unctuous, or essentially non-aqueous form willslowly hydrolyze when exposed to atmospheric moisture (or to acomposition GOH, where G is selected from the group hydrogen and loweralkyl of 1 to 6 carbon atoms) to its corresponding phenol,p-chloro-o-benzyl phenol. This phenol is an excellent bactericide,having phenol coefficients in the order of 150-200 againstStaphylococcus aureus and Eberthella typhosa.

It is especially noteworthy that the novel immonium salts of thisinvention - in particular those immonium salts corresponding toutilizable antibacterial phenolic compositions - will slowly hydrolyzeor decompose to their corresponding efficacious phenolic compositionwith moderation of the irritating effect of the phenol on tissue; butwith a slow, desirable, long lasting liberation of the antibacterialphenol.

Thus this invention also claims an antibacterial composition comprisingan efficacious amount of the immonium salt of Formula (I) incorporatedin a suitable vehicle.

To those skilled in the art it is obvious that the term "efficaciousamount" depends on the utility involved, the vehicle, and the efficiencyof the corresponding phenol; but, in general, the efficaciousconcentration of the immonium salt will correspond roughly to the knownefficacious concentration of the corresponding phenol, since phenols arewell established antibacterials. Thus antibacterial concentrations of0.001 to 50% of the immonium salt in a suitable vehicle are possible --in addition to its application alone, but concentrations of 0.01 to 10%are preferred, with concentrations of 0.1 to 1% most preferred.

The term "suitable vehicle" can vary according to the utility involved,and includes organic solvents, soaps, powders, detergents, creams, oils,organic/water emulsions, unctuous bases -- and other media dictated bythe utility involved.

This invention also claims a method for the control of bacteria whichcomprises applying to the locus to be treated an antibacterial amount ofthe immonium salt of Formula (I).

It is preferred to employ a solvent or solvents during the instant novelprocesses of this invention; however no solvent, or an excess of one ofthe reagents may be employed if desired.

The following examples are presented to describe the invention morefully without any intent of being limited thereby. All parts andpercentages are by weight, and all temperatures are in degreescentigrade unless otherwise specified.

EXAMPLE 1 -- PREPARATION OF p-CRESYL CHLOROFORMATE

A solution of 1100 parts of p-cresol in 4330 parts of toluene was cooledto -10° and 1500 parts of phosgene was condensed therein. Sodiumhydroxide solution (20%, 36.60 parts) was added slowly with stirringkeeping the temperature <0°. The product layer was separated, washedwith water, dried over sodium sulfate and the solvent removed bydistillation. The product was distilled through a Vigreaux column toyield 1230 parts (71%) of product boiling at 97°-100°/14 mm. of mercuryn₂₅ ^(D) =1.5100(Nuclear magnetic resonance spectra confirmed theidentity of the product).

EXAMPLE 2 -- PREPARATION OF 2,6 - XYLYL CHLOROFORMATE

This material was prepared in the same manner as the p-cresylchloroformate above using 373 parts of 2,6-xylenol and 483 parts ofphosgene. Distillation yielded 448 parts (81%) of product boiling at155°-157°/150 mm. of mercury, n₂₅ ^(D) =1.5023. Elemental analyses,infrared and nuclear magnetic resonance spectra confirmed the identityof the product.

EXAMPLE 3 -- PREPARATION OF α-CHLORO-p-CRESYL CHLOROFORMATE

A mixture of 1110 parts of p-cresyl chloroformate, 23.1 parts ofphosphorous trichloride and 2.3 parts benzamide was heated to 135°. Thetemperature was controlled at that point while a mixture of 12.3 partsof benzoyl peroxide and 999 parts of sulfuryl chloride was added over aperiod of six hours to the stirred reaction. When addition was completethe liquid residue was distilled through a Vigreaux column yielding 885parts (66%) of solid product boiling at 127°-130°/4.5 mm. of mercury;m.p. 60.5°-61.5°. Elemental analyses, infrared and nuclear magneticresonance spectra confirmed the identity of the product.

EXAMPLE 4 -- PREPARATION OF α-CHLORO-2,6 XYLYL CHLOROFORMATE ANDα,α'-DICHLORO-2,6-XYLYL CHLOROFORMATE

A mixture of 420 parts of 2,6-xylyl chloroformate, 17 parts ofphosphorous trichloride and 1.7 parts of benzamide was reacted at 135°over a period of six hours with a mixture of 7 parts of benzoyl peroxideand 740 parts of sulfuryl chloride. The liquid residue was carefullydistilled through a helix packed column. This yielded two majorfractions. One fraction boils at 135°-145°/10 mm. of mercury and yielded125 parts (25%) of α-chloro-2,6-xylyl chloroformate, n₂₅ ^(D) =1.5310.Elemental analyses, infrared and nuclear magnetic resonance spectraconfirmed the identity of the product.

A second fraction boiled at 162°-165°/10 mm. of mercury and yielded 143parts (25%) of α,α'-dichloro-2,6-xylyl chloroformate as a white solidmelting at 71.5°-73.5°. Elemental analyses, infrared spectra, andnuclear magnetic resonance spectra confirmed the identity of theproduct.

EXAMPLE 5 -- PREPARATION OF THE IMMONIUM SALT OF DIMETHYL FORMAMIDE ANDα-CHLORO-p-CRESYL CHLOROFORMATE

A mixture of 10.2 parts of α-chloro-p-cresyl chloroformate and 47 partsof dimethyl formamide was stirred for one half hour. There was avigorous reaction, gas evolved, and an orange precipitate formed. Theprecipitate was quickly filtered into a Soxhlet extractor and wasextracted for four hours with anhydrous ether. The solid was then pouredinto acetonitrile and the residual solid collected by suction filtrationin the absence of air. After drying, the material was a light coloredhygroscopic solid. Elemental analyses agreed with C₁₀ H₁₃ Cl₂ NO, whileinfrared and nuclear magnetic resonance spectra confirmed the identityof the product.

EXAMPLE 6 -- PREPARATION OF THE IMMONIUM SALT OF DIMETHYL FORMAMIDE ANDp-CRESYL CHLOROFORMATE

The process of Example 5 was repeated using p-cresyl chloroformate inthe same molar proportion as α-chloro-p-cresyl chloroformate.

Nuclear magnetic resonance spectra confirmed the identity of theproduct.

EXAMPLE 7 -- PREPARATION OF THE IMMONIUM SALT OF DIMETHYL FORMAMIDE ANDα,α'-DICHLORO-2,6-XYLYL CHLOROFORMATE

The process of Example 5 was repeated using α,α'-dichloro-2,6-xylylchloroformate in the same molar proportions as α-chloro-p-cresylchloroformate. The corresponding immonium salt was obtained in goodyield.

EXAMPLE 8 -- PREPARATION OF THE IMMONIUM SALT OF DIMETHYL FORMAMIDE ANDo-CRESYL CHLOROFORMATE

The process of Example 5 was repeated using o-cresyl chloroformate inthe same molar proportions as α-chloro-p-cresyl chloroformate. Thecorresponding immonium salt was obtained in good yield.

EXAMPLE 9 -- PREPARATION OF THE IMMONIUM SALT OF DIMETHYL FORMAMIDE ANDm-CRESYL CHLOROFORMATE

The process of Example 5 was repeated using m-cresyl chloroformate inthe same molar proportions as α-chloro-p-cresyl chloroformate. Thecorresponding immonium salt was obtained in good yield.

EXAMPLE 10 -- PREPARATION OF THE IMMONIUM SALT OF DIMETHYL FORMAMIDE ANDα-CHLORO-o-CRESYL CHLOROFORMATE

The process of Example 5 was repeated using α-chloro-o-cresylchloroformate. The corresponding immonium salt was obtained in goodyield.

EXAMPLE 11 -- PREPARATION OF THE IMMONIUM SALT OF DIMETHYL FORMAMIDE ANDα-CHLORO-m-CRESYL CHLOROFORMATE

The process of example 5 was repeated using α-chloro-m-cresylchloroformate. The corresponding immonium salt was obtained in goodyield.

EXAMPLE 12 -- PREPARATION OF p-CHLOROMETHYL PHENOL

Equimolar quantities of p-chloromethylphenyl chloroformate and dimethylformamide were reacted at room temperature for one hour in acetonitrile(590 parts acetonitrile for every mole of dimethyl formamide orp-chloromethylphenyl chloroformate). Equimolar quantities of methanolwere then added to the immonium salt mixture, and the solution was thenstirred for about one half hour (with cooling) at 25°-30°C.

Nuclear magnetic resonance spectra confirmed the existence ofp-chloro-methyl phenol in solution.

EXAMPLE 13 -- PREPARATION OF o-CHLOROMETHYL PHENOL

The process of Example 12 was followed using o-chloromethylchloroformate in the same molar proportions as p-chloromethylchloroformate.

The corresponding o-chloromethyl phenol was obtained in solution.

EXAMPLE 14 -- PREPARATION OF 2-METHYL-6-CHLOROMETHYL PHENOL

The process of Example 12 was followed, using2-methyl-6-chloromethyl-phenyl chloroformate in the same molarproportions as p-chloromethyl chloroformate. The corresponding2-methyl-6-chloromethyl phenol was obtained in solution.

EXAMPLE 15 -- PREPARATION OF 2,6-DICHLOROMETHYL PHENOL

The process of Example 12 was followed using 2,6-dichloromethyl phenylchloroformate in the same molar proportions as p-chloromethylchloroformate. The corresponding 2,6-dichloromethyl phenol was obtainedin solution.

EXAMPLE 16 -- PREPARATION OF p-METHOXYMETHYL PHENOL

The process of Example 12 was repeated but in this case excess methanol(1000 g. of methanol/mole of the immonium salt) was added. The reactionmixture was stirred for one hour, diluted with water, and extracted withether. After drying the product solution over sodium sulfate,evaporating the solvent, and trituration of the residue oil with hexane,p-methoxymethyl phenol was obtained in 78% yield, M.P. 79°-80°. Infraredand nuclear magnetic resonance spectra confirmed the identity of theproduct.

EXAMPLE 17 -- PREPARATION OF o-METHOXYMETHYL PHENOL

The process of Example 16 was essentially repeated using o-chloromethylphenyl chloroformate in the same molar proportions asp-chloromethylphenyl chloroformate. The corresponding product,o-methoxymethyl phenol, was obtained after fractionation; b.p. 70°/3 mm.of mercury, n₂₃ ^(D) 1.5355. Infrared and nuclear magnetic spectraconfirmed the identify of the product.

EXAMPLE 18 -- PREPARATION OF 3(4'-HYDROXYBENZYL)-2,4-PENTANEDIONE

A solution of p-chloromethyl phenol in acetonitrile (Example 12) wasreacted with equimolar dimethyl amine and equimolar 2,4-pentanedione bystirring together for one hour. The reactive mixture was diluted withwater, acidified with hydrochloric acid, extracted with ether, and thenthe ether extract was dried with sodium sulfate. The residual oil wastriturated with benzene to yield 78% of 3(4'hydroxybenzyl)-2,4-pentanedione, M.P. 93°-94.5°C. Infrared and nuclearmagnetic resonance spectra confirmed the identity of the product.

EXAMPLE 19 -- PREPARATION OF α-CYANO-p-CRESOL

A solution of p-chloromethyl phenol in acetonitrile (Example 12) wasreacted with equimolar sodium cyanide in excess methanol (800 partsmethanol/mole sodium cyanide) and the reaction mixture was refluxed forone hour. The oil after solvent evaporation (washed as in Experiment 18)was fractionated to yield 45% of α-cyano-p-cresol (b.p. 50°-155°/1 mm.of mercury; M.P. 68°-70°). Infrared spectra confirmed the identity ofthe product.

EXAMPLE 20 -- PREPARATION OF α-CYANO-o-CRESOL

The process of Example 19 was repeated using o-chloromethyl phenol inthe same molar proportions as p-chloromethyl phenol. Infrared spectraconfirmed the identity of the product.

EXAMPLE 21 -- PREPARATION OF 4-DIETHYLPHOSPHONOMETHYL PHENOL

A solution of p-chloromethyl phenol in acetonitrile (Example 12) wasreacted with equimolar methyl phosphite at about 50°. When theexothermic reaction had ceased the solvent was removed by distillationand the pot-temperature was raised to 175°. The product was dissolved inether, washed with water, dried with sodium sulfate, and the solventevaporated.

The product, 4-methylphosphonomethyl phenol, was obtained in 93% yield,M.P. 89°-91°.

The infrared and nuclear magnetic resonance spectra confirmed theidentity of the product.

EXAMPLE 22 -- PREPARATION OF 2-DIETHYLPHOSPHONOMETHYL PHENOL

The process of Example 21 was repeated using o-chloromethyl phenol inthe same molar proportions as p-chloromethylphenol.

The product was distilled in a moleculr still (95°-170°/7ω) in 99% yield(n₂₅ ^(D) 1.5150). Elemental analyses (C₁₁ H₁₇ C₁₄ P), infrared spectraand nuclear magnetic resonance spectra confirmed the identity of theproduct.

EXAMPLE 23 -- PREPARATION OF 2-METHYL-o-DIETHYLPHOSPHONOMETHYL PHENOL

The process of Example 21 was repeated using 2-methyl-o-chloromethylphenol in the same molar proportions as p-chloromethylphenol. Theproduct (100°-125°/1μ) was obtained in 74% yield.

Elemental analyses (C₁₂ H₁₉ O₄ P), infrared spectra, and nuclearmagnetic resonance spectra confirmed the identity of the product.

EXAMPLE 24 -- PREPARATION OF2-ETHOXY-2-OXO-7-DIETHYLPHOSPHONOMETHYL-4-5-BENZO-1-OXA-2-PHOSPHOLANE

The process of Example 21 was repeated using 2,6-dichloromethyl phenolin the same molar preparations as p-chloromethylphenol.

The product (165°-200°/1μ) was obtained in fair yield.

Elemental analyses (C₁₆ H₂₂ P₂ O₆), infrared spectra and nuclearmagnetic resonance spectra confirmed the identity of the product.

It is understood that the details provided in the foregoingspecification can be modified by those skilled in the art withoutdeparting from the scope of the invention.

What is claimed is:
 1. A process for preparing ##SPC13##which comprisesreacting ##SPC14## wherein at least one of the group a, b, c, d and e isα-haloalkyl and a, b, c, d and e are independently selected from thegroup consisting of hydrogen, hydrocarbyl, alkyl, α-haloalkyl, halogenand nitro; R is selected from the group consisting of hydrogen, alkyland aryl; R' and R" are independently selected from the group consistingof hydrogen and alkyl, and X is selected from the group consisting ofbromine, chlorine and fluorine; the alkyl, hydrocarbyl and α-haloalkylgroups being from one to thirty carbon atoms, and aryl is selected fromthe group phenyl and napthyl, with 0.1 to 100 times the stoichiometricproportion of GOH wherein G is alkyl of 1 to 6 carbon atoms at atemperature from ambient to reflux.
 2. A process in accordance withclaim 1 wherein ##SPC15##and R' and R" are alkyl groups of 1 to 6 carbonatoms.
 3. A process according to claim 1 which comprises reacting##SPC16##with methanol, wherein at least one of a, b and e isα-haloalkyl and a, b and e are independently selected from the groupconsisting of hydrogen, alkyl and α-haloalkyl, the alkyl and α-haloalkylbeing from 1 to thirty carbon atoms.
 4. The process of claim 1 whereinthe process is carried out in the presence of a nonreactive organicsolvent.
 5. The process of claim 4 wherein the solvent is selected fromthe group consisting of acetonitrile, benzene, toluene, cyclohexane andpropionitrile.
 6. The process of claim 4 wherein the solvent isacetonitrile.
 7. The process of claim 1 wherein R' and R" areindependently selected from the group consisting of hydrogen and alkylof 1 to 12 carbon atoms.
 8. The process of claim 1 wherein thehydrocarbyl and α-haloalkyl groups are from 1 to 12 carbon atoms.
 9. Theprocess of claim 1 wherein the hydrocarbyl and α-haloalkyl groups arefrom 1 to 6 carbon atoms.